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Abstract

Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is also associated with elevated insulin levels and insulin resistance. In animal models hepatic regeneration is associated with increased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To further our understanding of the regulation of IGFBP-1 in cirrhosis we have studied steady state levels of IGFBP-1 mRNA in human liver from three groups of patients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic liver transplantation (n=4); group 2, patients undergoing major liver resection with no histological evidence of chronic liver disease (n=4); and group 3, patients undergoing orthotopic transplantation for chronic liver failure (n=9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patients IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin.

IGFBP-1 mRNA was detectable in all the human liver samples with the greatest levels seen from the normal livers of group 2 patients. Insulin levels were elevated in the cirrhotic group 3 patients compared to a normal range as were IGFBP-1 levels. There was no relationship between circulating levels of IGFBP-1 and IGFBP-1 gene expression.

In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of insulin suggesting that there are factors other than insulin regulating IGFBP-1 gene expression.

Journal of Endocrinology (1994) 141, 377–382

SUMMARY

The binding characteristics of corticosterone by rat liver were studied by a displaceable binding technique. The binding of corticosterone to protein fractionated by gel filtration and density gradient centrifugation has been carried out as a preliminary determination of the nature of the binding sites. The results were analysed and showed three types of binding sites for corticosterone with the characteristic association constants at 0° of K ₁ = 1·2 × 10¹⁰, K ₂ = 1 × 10⁸ and K ₃ = 1 × 10⁴ 1./mole. Percentage displacement of corticosterone from the nuclear fraction did not differ significantly from that from tissue or the mitochondrial-microsomal fraction. The K ₁ and K ₂ sites persisted in separated buffer-soluble fractions but were destroyed on mild heating leaving only the K ₃ sites.

ABSTRACT

We have compared circulating and hepatic somatomedin (SM) activity in rats with diabetes or malnutrition of varying severity. Somatomedin activity was measured by the hypophysectomized rat costal cartilage bioassay. In both moderate diabetes and moderate malnutrition, mean serum SM activity was not significantly lower than normal (79 ± 13% (s.e.m.) and 95 ± 11% vs normal controls respectively). In contrast, liver perfusate SM activity was significantly reduced in both groups (51 ± 12% for moderate diabetes and 44 ± 12% for moderate malnutrition). Liver extract SM activity was also significantly decreased in both moderate diabetes and malnutrition (74 ± 4% and 75 ± 6% vs normal controls respectively). In severe diabetes and malnutrition, both liver and serum activities were low, consistent with previous reports. Our studies showed that liver SM activity fell in response to metabolic stress before a decrease in circulating levels occurred, supporting the concept that the liver regulates serum SM activity and growth in diabetes and malnutrition.

J. Endocr. (1984) 101, 257–261

The mode of uptake of l-[¹²⁵I]thyroxine by freshly isolated rat liver parenchymal cells was studied by a rapid centrifugation technique. Using conditions for measuring initial rates of uptake, uptake by liver cells was not saturable when exposed to hormone concentrations in the incubation medium ranging from 2 pmol/l to 10 μmol/l. The Arrhenius plot was linear from 2 to 37°C; the temperature coefficient was 1·4. The uptake of l-[¹²⁵I]thyroxine by liver cells was 35% when compared with that of l-[¹²⁵I]tri-iodothyronine. In the presence of 2·8% bovine serum albumin the rate of uptake of l-[¹²⁵I]thyroxine by liver cells was reduced by 90%. These results suggest that l-[¹²⁵I]thyroxine enters the rat liver parenchymal cell by simple diffusion and only the free hormone crosses the plasma membrane.

SUMMARY

After perfusion of newborn rabbit liver with [1,2-³H]cortisol two radioactive metabolites were isolated from the perfusate and identified as 3α,11β,17α,21-tetrahydroxy-5β-pregnan-20-one (THF) and 11β,17α,20β,21-tetrahydroxypregn-4-en-3-one (20β-dihydrocortisol). The amount of metabolites recovered in the perfusate of livers of 1-day-old animals was lower than when 11- to 12-day-old animals were used. The results suggest a relative deficiency in the liver of newborn rabbits of the enzyme reducing ring A and the 20-oxo group of cortisol.

SUMMARY

The following effects were observed in the liver of male rats in the first few days after adrenalectomy: the rate of thymidine incorporation into DNA was increased three- to fourfold in the 2 days after adrenalectomy. The mitotic index was increased 5·5-fold on the first day and 15-fold on the second day after the operation. The number of tetraploid cells rose from 40 to 68%. While the subsequent administration of cortisol, cortisone or corticosterone to the adrenalectomized animals reduced DNA synthesis to the normal level, testosterone and oestrone were without effect. It is suggested that liver growth is regulated by the concentration of corticosteroids in the blood.